Chapter 19 - Depth of Understanding

Discuss the differences between natural and semisynthetic penicillin, using structure and function as the foundation of your answer.

There are two forms of antibiotics, the natural form and its derivatives. In the case of the derivatives, the core structure of the agent is altered by changing the side chains found attached to the core. Changing a side chain does not guarantee that a functional antibiotic will be formed. In some cases the newly derived molecule may have an increased spectrum of activity. In other cases, the synthetic side chain may result in a diminution or loss of activity.
For example natural penicillin has a very narrow spectrum and reacts against only a small group of Gram-positive bacteria. Modifying penicillin to form ampicillin broadens the spectrum to include Gram-negative bacteria; whereas modifying it to carbenicillin or ticarcillin can broaden the spectrum to include Pseudomonas species. Existing semi-synthetic penicillins can be further modified to increase the efficiency of inhibiting bacterial growth. For example, ampicillin can be further modified to mezlocillin or azlocillin.

Evaluate the main targets used for antibiotics with regard to selective toxicity.

There are five main targets for antibiotics and each can be evaluated using the criteria of selective toxicity. Of the five targets the cell wall is the best with regard to selective toxicity as the target of antibiotic attack is peptidoglycan which is not present in human cells. The inhibition of metabolic pathways used for the production of folic acid is also selective since humans do not make folic acid but rather ingest it as part of their diet. The bacterial ribosome is also a selective target since it is different than the ribosomes seen in human cells. However the last two targets, the plasma membrane and the DNA, are not selectively toxic as these structures are the same in bacteria and in our cells.

Most infectious diseases are caused by viruses, but there are few effective antiviral drugs. Explain why.

Although most infectious diseases are caused by viruses, details of their lifecycles have only recently started to be understood in detail. Understanding the lifecycle is the first step in developing drugs. Viruses are difficult to grow in the lab so it is difficult to test the efficacy of antiviral drugs. Early testing of antiviral compounds was by trial and error which was inefficient. Better understanding of viral lifecycles and use of recombinant DNA techniques has led to more than 40 antivirals being developed since the 1990s. Before then there were only 10.
Viruses are challenging to treat because they are intracellular parasites and once they enter a host cell are difficult to damage without damaging the host cell — they mainly use host cell machinery to replicate. Furthermore, successful antiviral drugs must eliminate all virions because the escape of even one virion from an infected cell into the host’s blood could quickly restart the infectious cycle.